Tildrakizumab Delivers in Phase IIB PsA Study

MADRID — Tildrakizumab (Ilumya) offered superior efficacy and comparable safety versus placebo in patients with psoriatic arthritis (PsA), a researcher reported here.

Based on interim 6-month results from a phase IIB study, a significantly higher proportion of patients receiving any dose of tildrakizumab achieved a 90% reduction in Psoriasis Area and Severity Index (PASI90), and a 50% reduction in American College of Rheumatology response criteria (ACR50) versus placebo, according to Philip Mease, MD, of the Swedish Medical Center in Seattle.

In patients who received 200 mg tildrakizumab every 12 weeks, 79.6% achieved PASI75 versus 16.7% with placebo, while 50% achieved PASI90 versus 7.1% with placebo (P<0.0001), he reported at the European Congress on Rheumatology, the European League Against Rheumatism (EULAR) annual meeting.

Meas also reported that:

• 79.5% of 78 patients who received a 200-mg dose of tildrakizumab every 4 weeks achieved ACR20 (P<0.001)
• 77.2% of 79 patients who received a 200-mg dose every 12 weeks achieved ACR20 (P<0.001)
• 73.1% of 78 patients who received a 20-mg dose every 12 weeks achieved ACR20 (P<0.05)
• 71.4% of 77 patients who received a 100-mg every 12 weeks achieved ACR20 (P<0.05)

In addition, PASI75 was achieved by 64.2% of patients receiving tildrakizumab 200 mg every 4 weeks (P<0.0001); by 55.6% of patients assigned to 100 mg every 12 weeks (P<0.0001), and by 46.3% of patients receiving tildrakizumab 20 mg every 12 weeks (P<0.05).

“By week 24, all four dose categories of tildrakizumab were significantly more efficacious than placebo in treatment of joint and skin manifestations of psoriatic arthritis, including patient-related pain,” Mease said. “There was a clear separation between tildrakizumab and placebo as early as 8 weeks.”

Tildrakizumab is a high-affinity, humanized, monoclonal antibody targeting interleukin (IL) 23p19. It is currently FDA approved to treat moderate-to-severe plaque psoriasis.

The 24-week, randomized, double-blind, placebo-controlled, multiple-dose study included 391 adults with PsA who had three or more tender and three or more swollen joints. Patients were randomized (1:1:1:1:1) to receive tildrakizumab 200 mg every 4 weeks, 200 mg, 100 mg, or 20 mg every 12 weeks, or placebo every 4 weeks. Stable concomitant methotrexate or leflunomide use was permitted but not required.

The best response of the active treatments was with tildrakizumab 200 mg every 4 weeks with 52.6% of patients achieving ACR50 (P<0.001), Mease stated. Also, ACR70 was achieved by 29.1% of patients given 200 mg every 4 weeks (P<0.05), by 22.1% given 100 mg every 12 weeks (P<0.05), and by 10.1% of placebo patients.

Half of the patients had better PASI90 scores with 200 mg every 12 weeks (P<0.0001), as did 47.2% on 200 mg every 4 weeks (P<0.0001), 38.9% on 100 mg every 12 weeks (P<0.001), and 36.6% on 20 mg every 12 weeks (P<0.05) versus 7.1% on placebo.

While the response rates improved with increasing dose, shortening of dosing interval of 200 mg from 12 to 4 weeks did not result in a measurable increase in skin or joint response score, Mease and colleagues found.

In terms of adverse events (AEs), serious AEs occurred in 2.2% of tildrakizumab-treated patents and 2.5% of placebo-treated patients. Treatment-related serious AEs occurred in 0.3% of tildrakizumab-treated patients (as judged by the investigator). The most frequent AEs included nasopharyngitis and diarrhea with no reports of candidiasis, inflammatory bowel disease, major adverse cardiac events, or malignancy. No patients discontinued treatment due to AEs and no deaths were reported.

EULAR press conference moderator and program chair Thomas Dörner, MD, of the University Hospital Charite in Berlin, noted that “The challenge in psoriatic arthritis is that we need drugs that are effective on the joints and on the skin.”

“With prior drugs, we have seen some distinctions. Some are very good on the joints, some of them are very good on the skin, but are less effective in the counter condition,” he told MedPage Today. “With the p19 antibodies that block IL-23, the promise is that they have favorable combined effects on joint and skin. Tildrakizumab, at least from this phase II data, is along this expectation.”

Mease pointed out that, despite the “laundry list of drugs” for PsA, these agents often lose efficacy over time, or may have serious side effects, so “it is good to have more choices to reduce the morbidity and mortality of this disease.”